ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.522G>C (p.Trp174Cys)

dbSNP: rs1064793237
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479816 SCV000565430 likely pathogenic not provided 2013-03-01 criteria provided, single submitter clinical testing The W174C missense substitution in the PRPH2 (aka RDS) gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The W174C amino acid substitution is non-conservative with a non-polar residue (Trp) being replaced by a polar reside (Cys), which may also affect disulfide bonds. The Human Gene Mutation database reports that many missense variants (G170S, R172Q, R172G, R172W, D173V, Q178R, W179R) have been reported in neighboring codons in association with PRPH2-related disorders. The residue at which this substitution occurs is highly conserved in the Peripherin-2 protein and in related proteins. An external variant database reports that W174C was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Therefore, this is a good candidate for a pathogenic variant, although the possibility that it is a benign polymorphism cannot be excluded.
Blueprint Genetics RCV001075073 SCV001240684 uncertain significance Retinal dystrophy 2018-07-05 criteria provided, single submitter clinical testing
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001250369 SCV001424702 likely pathogenic Retinitis pigmentosa 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.522G>C in the PRPH2 gene has not been reported to our knowledge . We found this variant in 1 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is not listed in dbSNP and/or HGMD. It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PP3, PP5] and classified NM_000322.4:c.522G>C in the PRPH2 gene as a Likely Pathogenic mutation.
Leiden Open Variation Database RCV000479816 SCV001745066 uncertain significance not provided 2021-04-06 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters.

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